Genetic Variant NM_031944.3:c.76G>A (chr1-226223757-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031944.3(MIXL1):c.76G>A(p.Gly26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,270,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G26C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

MIXL1
NM_031944.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.476

Publications

0 publications found

Variant links:

Genes affected

MIXL1 (HGNC:13363): (Mix paired-like homeobox) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including endodermal cell differentiation; hematopoietic progenitor cell differentiation; and positive regulation of mesoderm development. Predicted to act upstream of or within cell migration involved in gastrulation and hemopoiesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIXL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16292429).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	NM_031944.3	MANE Select	c.76G>A	p.Gly26Ser	missense	Exon 1 of 2	NP_114150.1	Q9H2W2-1
	MIXL1	NM_001282402.2		c.76G>A	p.Gly26Ser	missense	Exon 1 of 2	NP_001269331.1	Q9H2W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIXL1	ENST00000366810.6	TSL:1 MANE Select	c.76G>A	p.Gly26Ser	missense	Exon 1 of 2	ENSP00000355775.4	Q9H2W2-1
	MIXL1	ENST00000542034.5	TSL:1	c.76G>A	p.Gly26Ser	missense	Exon 1 of 2	ENSP00000442439.1	Q9H2W2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000157

AC:

AN:

1270334

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

624546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25766

American (AMR)

AF:

0.00

AC:

AN:

22042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20756

East Asian (EAS)

AF:

0.00

AC:

AN:

27278

South Asian (SAS)

AF:

0.00

AC:

AN:

65268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.00000196

AC:

AN:

1022480

Other (OTH)

AF:

0.00

AC:

AN:

51890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.90

PhyloP100

-0.48

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.67

REVEL

Benign

0.19

Sift

Benign

0.14

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.11

MutPred

0.18

Gain of glycosylation at G26 (P = 1e-04)

MVP

0.23

MPC

0.52

ClinPred

0.078

GERP RS

-0.43

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.043

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over